Volatile anesthetics are commonly used to achieve the appropriate plane of anesthesia in human and veterinary surgical patients. Volatile anesthetics are however costly and have certain side effects such as reducing vascular resistance and resulting hypotension. It therefore can be desirable to reduce the amount, typically determined as minimum alveolar concentration or “MAC”, of the volatile anesthetic needed during painful procedures through use of a MAC reducing agent. Known MAC reducing agents include opiates such as morphine and fentanyl, ketamine, lidocaine and dexmedetomidine.
Opioid compounds in particular are capable of dramatic MAC reductions of 50% and higher. For example, morphine is currently used as a standard MAC reduction agent in the veterinary field. The use of morphine and other opioids however incurs numerous disadvantages related to the fact that these substances are highly addictive and thus are classified as controlled substances under DEA regulations. Use of these substances requires a license from the DEA to use, and are subject to additional strict control measures including secure storage under lock and key, and detailed logging of when and how each dose is used or disposed. Routine maintenance of opioids in a clinic runs the risk of abuse by anyone with access to the supply including veterinary clinic staff members, and the risk of break-in and theft of the substances by anyone else seeking unlawful use. Additionally, morphine and other opioids commonly used for pain management in veterinary medicine often induce undesirable mental and behavioral changes in certain animals including dogs, including for example lethargy and dysphoria. Other side effects associated with morphine and other opioids in dogs and other species include a decrease in gastrointestinal motility and increase in incidence of complications such as constipation, increase in urinary retention which predisposes to damage of the urinary tract, and depression of the respiratory or cardiovascular system, which can be especially dangerous for neonatal and juvenile and geriatric patients. A need therefore remains for improved methods for managing visceral pain during surgical procedures requiring general anesthesia and improved methods for MAC reduction.
The neurokinin-1 (NK-1) receptor is a receptor for the neurotransmitter substance P, and is distributed throughout the central nervous system. Certain neurokinin-1 (NK-1) receptor antagonists are known as having antidepressant, anxiolytic, and antiemetic properties. In particular, the NK-1 receptor antagonist aprepitant has provided a valuable tool for clinical management of the nausea and vomiting associated with cancer chemotherapy. The NK-1 receptor antagonist maropitant (available from Pfizer as Cerenia®), is an NK-1 receptor antagonist that is approved for use as an antiemetic in dogs.